Acetyl-L-Carnitine is an natural ester of the amino acid L-carnitine that is produced in everyone's body.  It works primarily by helping the energy production of the body in each cells mitochondria more efficient.  It is available without a prescription as a natural supplement.  The four studies using it are all from in Italy and only one, but a large one, is a recent study.  It has been used mostly with elderly depressed patients.  

The carnitines have now been found helpful in 27 different double-blind studies for various human diseases.  Because of this, I have started trying out acetyl-L-carnitine on selected patients who are depressed and suffer from some of the other diseases helped, e.g. chronic fatigue syndrome, erectile dysfunction, intermittent claudication, heart disease, etc.  See the carnitines.  The cost is as low as $8-$16 per month if the bulk powder is purchased in 1000 g bags for $133 a bag.  Capsules run $20-$70 per month.

It can cause diarrhea in some patients with at least one 59 year old patient of mine developing microscopic colitis which cleared with treatment.  Overall side-effects are less than prescription anti-depressants.

Acetyl-L-Carnitine: Two Depression Studies with Elderly: Two small DB PC studies, both were done in Italy, one at a VA hospital of 28 patients 70-80 years old with depression (300.40 DSM-IIIR) with 500 mg t.i.d. and one at a lesser university, Univ. Catania of 60 senile dysthymic patients for 60 days with 3 g/d found benefit. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Garzya G, Corallo D, Fiore A, Lecciso G, Petrelli G, Zotti C. Drugs Exp Clin Res. 1990;16(2):101-6; Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders. Bella R, Biondi R, Raffaele R, Pennisi G. Int J Clin Pharmacol Res. 1990;10(6):355-60. Ed: The cheapest ALC on the internet in Dec. 2003 was $25 for 120 500mg tabs.  The monthly cost of $20-$80 per month is on the high side although not unreasonable if it really worked. 

Acetyl-L-Carnitine Promoted for Elderly Depression: In a very poor, very small open trial of just two mildly depressed elderly men, Univ of Pittsburgh researchers suggest that ALCAR helps depression because elevated phosphomonoesters in the pre-frontal lobes decreased in both after 12 weeks of treatment and the decrease correlated with a decrease in HAM-D depression scores. 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results. Pettegrew JW, Levine J, Gershon S, Stanley JA, Servan-Schreiber D, Panchalingam K, McClure RJ. Bipolar Disord. 2002 Feb;4(1):61-6; Pettegrew also claims that DB PC research shows that ALC helps both Major Depressive Disorder and Alzheimer's disease. Mol Psychiatry. 2000 Nov;5(6):616-32. Ed: Pettegrew goes far beyond what his research shows.  Still, I think that ALCAR may prove to be of value for mild cognitive impairment and depression in the elderly and even depression with severe fatigue in younger adults.  In view of its low cost and very few side-effects, I think it is fine to try out.  If you improve, that's not proof that it helped.  You need a much larger study to prove cause-effect.  But if you improve, I would keep taking it.  I have been prescribing it to patients, a number of whom have reported feeling better after starting it.

Acetyl-L-Carnitine Helped Chronic Depression: In a 12-week DB PC study of 204 patients with dysthymia, long-lasting depression, acetyl-L-carnitine (ALCAR) 500 mg b.i.d. did as well as the atypical antipsychotic amisulpride 50 mg b.i.d. with patients in both groups showing considerable improvement. A double-blind, randomised, controlled clinical trial of acetyl-l-carnitine vs. amisulpride in the treatment of dysthymia. Zanardi R, et al. Vita-Salute University San Raffaele, Milan, Italy. Eur Neuropsychopharmacol 2005 Nov 25. Ed: Amisulpride has been shown better than placebo in at least 3 double-blind studies (Int Clin Psychopharm 2002 Dec) and better than sertraline in one study. However, it is an odd choice for this study, since it is not primarily an anti-depressant. I, myself, have tried using it or carnitine in a couple patients with very severe fatigue and moderate depression.

Acetyl-L-Carnitine: Depression in Elderly Helped by ALCAR: In a small cross-over study of 24 elderly admitted because of depression, ALCAR for 1 month was "highly effective" for depression, but general somatic symptoms as well as anxiety, asthenia and sleep disturbances didn’t improve. L-acetylcarnitine in depressed elderly subjects. A cross-over study vs placebo. Tempesta E, Casella L, et al., Catholic University of the Sacred Heart, Rome, Italy. Drugs Exp Clin Res. 1987;13(7):417-23.